Fragile X syndrome, the most common form of inheritable mental retardation, results from the loss of function of the fragile X mental retardation protein (FMRP). FMRP is a selective RNA-binding protein shown to effect the translation and translocation of mRNA in the brain. Recently, FMRP has been shown to associate with the microRNA pathway. However, the molecular mechanisms controlling the activity of FMRP to effect translation remain elusive. The aims of this proposal are: 1) to determine the effects of FMRP on the expression levels of microRNA, and in particular let-7b, during brain development and 2) to determine the existence of a coordinated role of microRNA and FMRP to suppress translation. To examine these aims, MAPI B will be used as the experimental model due to preliminary data showing that both FMRP and microRNA can regulate the protein levels of MAP1B in the brain. By determining these mechanisms, a clearer understanding and potential, novel therapeutic targets of fragile X syndrome will be obtained, along with an improved understanding of FMRP's role in normal brain development. [unreadable] [unreadable]